Hepatocytes-activity-distribution

The proposed set of functions are able to perform a statistical analysis of the data available from The bioIVT(R) database. The analysis is performed using the activity ditribution (pmol/min/Mio cells) from CYPs:

  • CYP2A6: coumarin
  • CYP2B6: bupropion
  • CYP2C8: amodiaquine
  • CYP2C9: tolbutamide
  • CYP2C19: mephenytoin
  • CYP2D6: dextromethorphan
  • CYP2E1: chlorzoxazone
  • CYP3A4(tests.): testosterone
  • CYP3A4(MDZ): midazolam

Additional analysis were reported for UGT1A1, ST (using 7-hydroxycoumarin), and AO

The analysis needs the input dataset structure reported in the input file from https://bioivt.com/inventory?facets=%28productType%3A%22Cell+Products%22%29&facets=%28species.lvl0%3A%22Human%22%29&facets=%28matrix%3A%22Hepatocyte+-+Cryoplateable%22%29&string=Cryoplateable (after login). The user needs to provide an input file as csv with the column names of the probe substrate as reported in setnames (line 36). The script automatically returns for each isoform:

  • The number of male and female donors investigate for the given isoform
  • The median, mean, SD, the p value for the Shapiro normality assessment, the Barlett's test outcome (homogeneity of the variance between male and female), and the Hartigian's test to evaluate the unimodal distribution
  • The mean and the SD in logarithmic domain
  • The median, mean, SD, best lambda, the p value for the Shapiro normality assessment for male and female, the Barlett's test and the p value from the ANOVA test after the Box-Cox transformation.

Examples cases of the system parameters impact

The code report the simulations reported in the tutorial in order to explore the impact of the:

  • Surface area and volume of the apical side in the transwell of a Gut-Liver OoC.
  • Volume samling and evaporation.

In the codes are available the input data and the output reported as figures in the MS.